title: Sildenafil increases serum testosterone levels by a direct action on the testes.
abstract: Phosphodiesterase-5-inhibitors, such as sildenafil, increase intracavernosal cyclic guanosine monophosphate levels, which results in corporal smooth muscle relaxation and penile erection. Here, we determined the effects of sildenafil administration on the hypothalamic-pituitary-gonadal axis in men with erectile dysfunction and low testosterone levels. The Testosterone and Erectile Dysfunction trial (ClinicalTrials.gov # NCT00512707) initially administered an optimized dose of sildenafil to 140 men, aged 40-70 years with erectile dysfunction, low serum total testosterone (<11.4 nmol/L; 330 ng/dL) and/or free testosterone (<173 pmol/L; 50 pg/mL) over 3-7 weeks. Sex steroids and gonadotropins were measured at baseline and after sildenafil optimization in a longitudinal study without a separate control group. Serum testosterone, dihydrotestosterone (DHT) and oestrogens were measured using liquid chromatography-tandem mass spectrometry. Administration of an optimized dose of sildenafil was associated with mean increases of 3.6 nmol/L (103 ng/dL; p < 0.001) and 110 pmol/L (31.7 pg/mL; p < 0.001) in total and free testosterone levels respectively. This was accompanied by parallel increases in serum DHT (0.17 nmol/L; 4.9 ng/dL; p < 0.001) and oestradiol (14 pmol/L; 3.7 pg/mL; p < 0.001) and significant suppression of luteinizing hormone (change -1.3 units/L; p = 0.003) levels, suggesting a direct effect at the testicular level. Androstenedione and oestrone increased by 1.3 nmol/L (38 ng/dL; p = 0.011) and 10.7 pmol/L (2.9 pg/mL; p = 0.012), respectively, supporting a possible effect of sildenafil on adrenal steroidogenesis. In conclusion, sildenafil administration was associated with increased testosterone levels likely ascribable to a direct effect on the testis.
authors.affiliation: Valley Medical Group, Endocrinology Department, Greenfield Health Center, Greenfield, MA, USA.
authors.forename: M
authors.initials: M
authors.lastname: Spitzer
authors.forename: S
authors.initials: S
authors.lastname: Bhasin
authors.forename: T G
authors.initials: TG
authors.lastname: Travison
authors.forename: M N
authors.initials: MN
authors.lastname: Davda
authors.forename: H
authors.initials: H
authors.lastname: Stroh
authors.forename: S
authors.initials: S
authors.lastname: Basaria
mesh_terms: D000328:Adult; D000368:Aged; D000735:Androstenedione / Q000097:blood; D013196:Dihydrotestosterone / Q000097:blood; D007172:Erectile Dysfunction / Q000097:blood / Q000188:drug therapy; D004958:Estradiol / Q000097:blood; D004970:Estrone / Q000097:blood; D006801:Humans; D007986:Luteinizing Hormone / Q000097:blood; D008297:Male; D008875:Middle Aged; D058986:Phosphodiesterase 5 Inhibitors / Q000627:therapeutic use*; D010879:Piperazines / Q000627:therapeutic use*; D011687:Purines / Q000627:therapeutic use; D000068677:Sildenafil Citrate; D013450:Sulfones / Q000627:therapeutic use*; D013737:Testis / Q000187:drug effects*; D013739:Testosterone / Q000097:blood*
chemical_list: D058986:Phosphodiesterase 5 Inhibitors; D010879:Piperazines; D011687:Purines; D013450:Sulfones; D013196:Dihydrotestosterone; D004970:Estrone; D013739:Testosterone; D000735:Androstenedione; D004958:Estradiol; D007986:Luteinizing Hormone; D000068677:Sildenafil Citrate
keywords: erectile dysfunction; selective phosphodiesterase-5 inhibitors; sildenafil; testosterone